Study says genes alter sensitivity to alcohol

An experiment by a Yale research team suggests those who do not seem to know when to stop drinking may have someone besides themselves to blame — their parents. The research holds more than excuses, however, and may provide a key to reducing incidences of alcoholism.

Using a chemical that induces effects similar to those of alcohol, psychiatry professor Dr. Ismene Petrakis, along with a team of scientists, showed that people with a family history of alcoholism tend to have a receptor that is less sensitive to alcohol than that of people with no familial history. A low sensitivity to alcohol could cause people to drink more, putting them at higher risk of addiction.

In the study, ketamine — an anesthetic — or placebos were administered to two groups of participants, one of which was composed of subjects with a family history of alcoholism. All of the participants were healthy non-alcoholics. The researchers observed a lower sensitivity to ketamine’s intoxicating effects in the participants with a familial history of alcoholism.

Ketamine targets a brain receptor that also binds with alcohol. The study provided evidence that people with a familial history of alcoholism may be less sensitive to alcohol’s effects. Such a person’s inability to recognize the warning signs of intoxication could promote heavy drinking, leading to addiction.

The experiment’s results imply there is a physiological difference between the receptors of those with and without familial alcoholism.

“Our research has focused on teasing out what the mechanism that underlies some of these differences might be,” said Petrakis.

Previous experiments had suggested that alcohol-dependent patients had altered receptor density or function, and the new research provides strong evidence that the cause of such alteration is genetic.

The team plans to conduct another experiment to confirm its results. It will use molecular analysis and psychiatry to investigate candidate genes that may affect the receptor, said Dr. John Krystal MED ’84, who leads the Center for the Translational Neuroscience of Alcoholism.

“We are all working together at different levels to try to understand, in a more specific way, and in hopefully a more deep way, how particular genes produce a risk for alcoholism,” he said.

The research could lead to better treatments for alcoholism. Valium, a common treatment for alcohol withdrawal, targets a family of receptors, including receptors that are responsible for the drug’s harmful side effects. A more specific medication targeting only the necessary receptors would be more effective, Krystal said.

Not all members of the scientific community agree with Petrakis’ conclusions. Dr. Phil Brewer, a professor of emergency medicine at Yale, said he believes that the focus of alcoholism research should be on the environment rather than the individual. Environmental factors include low taxes on alcohol and the promotion of alcohol abuse as a social norm.

“I don’t feel that there is a whole lot to be gained by studies showing the genetic basis for alcoholism,” Brewer said. “The most effective, though neglected, approach is the environmental approach.”

Brewer is the former medical director of South Central Rehabilitation Center, which focused on alcohol victims.

Medicine aside, the receptor research also has philosophical ramifications for the way the public views the issue, Petrakis said.

“There’s still some stigma for alcoholics that somehow being alcoholic is a matter of will,” she said. “This and other studies show that there are other factors at work in the development of alcoholism.”